Eruptive melanocytic naevi following initiation of elexacaftor/ivacaftor/tezacaftor for cystic fibrosis.

A 29 year old woman with cystic fibrosis (CF) presented to CF clinic following the sudden development of over 200 pigmented naevi located predominately on the trunk and limbs 3 months after commencing elexacaftor/tezacaftor/ivacaftor, a novel triple-therapy CFTR modulator therapy for CF. Skin biopsy confirmed benign naevi and the clinical presentation was consistent with eruptive melanocytic naevi. Elexacaftor/tezacaftor/ivacaftor received marketing authorisation in August 2020 and this is the first report of associated naevi. The individual described here remains clinically well, and continues on elexacaftor/tezacaftor/ivacaftor with dermatology follow-up.

CXCR2 inhibition enables NASH-HCC immunotherapy.

OBJECTIVE: Hepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data suggests NASH-HCC may be less sensitive to conventional immune checkpoint inhibition (ICI). We hypothesised that targeting neutrophils using a CXCR2 small molecule inhibitor may sensitise NASH-HCC to ICI therapy. DESIGN: Neutrophil infiltration was characterised in human HCC and mouse models of HCC. Late-stage intervention with anti-PD1 and/or a CXCR2 inhibitor was performed in murine models of NASH-HCC. The tumour immune microenvironment was characterised by imaging mass cytometry, RNA-seq and flow cytometry. RESULTS: Neutrophils expressing CXCR2, a receptor crucial to neutrophil recruitment in acute-injury, are highly represented in human NASH-HCC. In models of NASH-HCC lacking response to ICI, the combination of a CXCR2 antagonist with anti-PD1 suppressed tumour burden and extended survival. Combination therapy increased intratumoural XCR1+ dendritic cell activation and CD8+ T cell numbers which are associated with anti-tumoural immunity, this was confirmed by loss of therapeutic effect on genetic impairment of myeloid cell recruitment, neutralisation of the XCR1-ligand XCL1 or depletion of CD8+ T cells. Therapeutic benefit was accompanied by an unexpected increase in tumour-associated neutrophils (TANs) which switched from a protumour to anti-tumour progenitor-like neutrophil phenotype. Reprogrammed TANs were found in direct contact with CD8+ T cells in clusters that were enriched for the cytotoxic anti-tumoural protease granzyme B. Neutrophil reprogramming was not observed in the circulation indicative of the combination therapy selectively influencing TANs. CONCLUSION: CXCR2-inhibition induces reprogramming of the tumour immune microenvironment that promotes ICI in NASH-HCC.

Squamomelanocytic tumor: an unusual and distinctive entity of uncertain biological potential.

We report a case of a squamomelanocytic tumor of the skin. Clinically, the lesion was felt to be a melanocytic or vascular tumor but histologically was characterized by epithelioid cells with focal squamous differentiation. Immunohistochemical staining showed that half of cells stained with MNF116 and a smaller proportion stained with S100 and Melan A. A third population did not stain with either set of antigens. The lesion has some similarities to a melanocytic matricoma but no evidence of matrical differentiation. The biological potential of this distinctive tumor is not known because so few have been reported.

Squamous cell carcinoma developing in a naevus sebaceous of Jadassohn.

Squamous cell carcinoma developing within a naevus sebaceus of Jadassohn is rare. We report the fifth such case in the English literature to highlight the importance of early excision of any naevus sebaceus of Jadassohn with a history of change. Other cases have been reported, but the clinical and histopathological details were not well documented.

Frontal fibrosing alopecia associated with cutaneous lichen planus in a premenopausal woman.

A 45-year-old premenopausal woman presented with an 18-month history of a band-like area of fibrosing alopecia affecting the frontoparietal scalp. She also had marked thinning of the eyebrows. The histopathology was consistent with frontal fibrosing alopecia (FFA). Several months later she developed multiple pruritic papules on the wrists and feet. The clinical presentation and histopathology were consistent with cutaneous lichen planus. Although FFA has been reported to occur with mucosal lichen planus this is the first reported case of FFA associated with cutaneous lichen planus. This provides further evidence that FFA is a variant of lichen planopilaris.